The present invention relates to a method for making 2-fluoro-2-deoxy-D-glucose or [.sup.18 F]2FDG, utilizing an anion exchange resin. More particularly, the present invention relates to the use of an anion exchange resin to more effectively trap [.sup.18 F]fluoride ion, involving the treatment of the anion exchange resin having an anion, such as a carbonate or bicarbonate anion, with an aqueous solution of [.sup.18 F]fluoride ion target water and an alkali metal carbonate or bicarbonate salt, such as sodium bicarbonate.
Prior to the present invention, various procedures were used for making [.sup.18 F]2FDG, which is used as a radiopharmaceutical for Positron Emission Tomography (PET). Considerable effort has been expended in the development and refinement of such procedures. Because [.sup.18 F]fluoride ion has a low decay energy, (0.64 MEV), it allows the highest inherent resolution during PET measurements and has a relatively convenient half life of 109.7 min. The following equation illustrates the preferred procedure for making [.sup.18 F]2FDG starting with a solution of 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-.beta.-D-mannopyranose or "triflate": ##STR1## where Ac is acetate, and "PTR" means phase-transfer reagent.
One method of synthesizing [.sup.18 F]2FDG by the above procedure is shown by Hamacher et al., Journal of Nuclear Medicine, 27:235-238, (1986). Hamacher et al. employ an aminopolyether [Kryptofix 222 or K222]-potassium carbonate complex as a phase-transfer catalyst for [.sup.18 F]fluoride. An additional procedure for making [.sup.18 F]2FDG is shown by Brodack et al., Applied Radiation and Isotope, Volume 39, No. 7, pages 699-703 (1988) involving the employment of a tetrabutylammonium hydroxide as a phase-transfer catalyst in place of the aminopolyether potassium complex of Hamacher et al. Although Brodack et al. disclose that the triflate reacts with [.sup.18 F]fluoride ion using the tetrabutylammonium counter ion, a yield of 12-17% is reported which is significantly below the level considered acceptable for commercial robotic production of [.sup.18 F]2FDG.
The above procedures utilizing a phase-transfer reagent for [.sup.18 F]2FDG synthesis have an inherent disadvantage particularly if Kryptofix 222 is used as the phase-transfer catalyst. Kryptofix is toxic and minor traces of the phase-transfer catalyst are often difficult to remove from the final patient dose. Elaborate methods have to be used therefore to eliminate any traces of the phase-transfer catalyst before it is used. The application of automation using such PTR is therefore rendered more difficult.
An improvement in the use of a phase-transfer catalyst for making [.sup.18 F]2FDG is shown by Johnson et al., U.S. Pat. No. 5,169,942, which utilizes a less toxic PTR, such as a tetraalkylammonium bicarbonate. However, it has been found desirable to minimize any traces of the PTR from the final dose before intravenous use which complicates the implementation of this procedure.
As shown by S. A. Toorongian et al., cited below, alternative methods for making [.sup.18 F ]2FDG are also known which utilize an anion exchange resin to trap the [.sup.18 F]fluoride ion. However, the yields of [.sup.18 F]2FDG made by the anion exchange resin procedure have been found to be significantly less than methods employing a PTR. It would be desirable therefore to provide a procedure for improving the yield of [.sup.18 F]2FDG by using an anion exchange resin to more effectively trap the [.sup.18 F]fluoride ion and improve the yields of [.sup.18 F ]2FDG.